page_title: Nazarov cyclization reaction
section_title: Silicon-directed cyclization
hierarchical_section_title: Nazarov cyclization reaction / Modern variants / Silicon-directed cyclization
caption_attribution_description: English: silicon directed nazarov cyclization
context_page_description: The Nazarov cyclization reaction is a chemical reaction used in organic chemistry for the synthesis of cyclopentenones. The reaction is typically divided into classical and modern variants, depending on the reagents and substrates employed. It was originally discovered by Ivan Nikolaevich Nazarov in 1941 while studying the rearrangements of allyl vinyl ketones.
  As originally described, the Nazarov cyclization involves the activation of a divinyl ketone using a stoichiometric Lewis acid or protic acid promoter. The key step of the reaction mechanism involves a cationic 4π-electrocyclic ring closure which forms the cyclopentenone product. As the reaction has been developed, variants involving substrates other than divinyl ketones and promoters other than Lewis acids have been subsumed under the name Nazarov cyclization provided that they follow a similar mechanistic pathway.
  The success of the Nazarov cyclization as a tool in organic synthesis stems from the utility and ubiquity of cyclopentenones as both motifs in natural products and as useful synthetic intermediates for total synthesis. The reaction has been used in several total syntheses and several reviews have been published.
context_section_description: The earliest efforts to improve the selectivity of the Nazarov cyclization took advantage of the β-silicon effect in order to direct the regioselectivity of the elimination step. This chemistry was developed most extensively by Professor Scott Denmark of the University of Illinois, Urbana-Champaign in the mid-1980s and utilizes stoichiometric amounts of iron trichloride to promote the reaction. With bicyclic products, the cis isomer was selected for to varying degrees.
  The silicon-directed Nazarov cyclization reaction was subsequently employed in the synthesis of the natural product Silphinene, shown below. The cyclization takes place before elimination of the benzyl alcohol moiety, so that the resulting stereochemistry of the newly formed ring arises from approach of the silyl alkene anti to the ether.
caption: Silicon-directed Nazarov cyclization
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